Diffusion-weighted Imaging Fluid-attenuated Inversion Recovery Research Articles

Segmenting Ischemic Penumbra and Infarct Core Simultaneously on Non-Contrast CT of Patients with Acute Ischemic Stroke Using Novel Convolutional Neural Network.

Differentiating between a salvageable Ischemic Penumbra (IP) and an irreversibly damaged Infarct Core (IC) is important for therapy decision making for acute ischemic stroke (AIS) patients. Existing methods rely on Computed Tomography Perfusion (CTP) or Diffusion-Weighted Imaging-Fluid Attenuated Inversion Recovery (DWI-FLAIR). We designed a novel Convolutional Neural Network named I2PC-Net, which relies solely on Non-Contrast Computed Tomography (NCCT) for the automatic and simultaneous segmentation of the IP and IC. In the encoder, Multi-Scale Convolution (MSC) blocks were proposed to capture effective features of ischemic lesions, and in the deep levels of the encoder, Symmetry Enhancement (SE) blocks were also designed to enhance anatomical symmetries. In the attention-based decoder, hierarchical deep supervision was introduced to address the challenge of differentiating between the IP and IC. We collected 197 NCCT scans from AIS patients to evaluate the proposed method. On the test set, I2PC-Net achieved Dice Similarity Scores of 42.76 ± 21.84%, 33.54 ± 24.13% and 65.67 ± 12.30% and lesion volume correlation coefficients of 0.95 (p < 0.001), 0.61 (p < 0.001) and 0.93 (p < 0.001) for the IP, IC and IP + IC, respectively. The results indicated that NCCT could potentially be used as a surrogate technique of CTP for the quantitative evaluation of the IP and IC.

In Mild and Moderate Acute Ischemic Stroke, Increased Lipid Peroxidation and Lowered Antioxidant Defenses Are Strongly Associated with Disabilities and Final Stroke Core Volume.

In acute ischemic stroke (AIS), there are no data on whether oxidative stress biomarkers have effects above and beyond known risk factors and measurements of stroke volume. This study was conducted in 122 mild-moderate AIS patients and 40 controls and assessed the modified ranking scale (mRS) at baseline, and 3 and 6 months later. We measured lipid hydroperoxides (LOOH), malondialdehyde (MDA), advanced oxidation protein products, paraoxonase 1 (PON1) activities and PON1 Q192R genotypes, high density lipoprotein cholesterol (HDL), sulfhydryl (-SH) groups), and diffusion-weighted imaging (DWI) stroke volume and fluid-attenuated inversion recovery (FLAIR) signal intensity. We found that (a) AIS is characterized by lower chloromethyl acetate CMPAase PON1 activity, HDL and -SH groups and increased LOOH and neurotoxicity (a composite of LOOH, inflammatory markers and glycated hemoglobin); (b) oxidative and antioxidant biomarkers strongly and independently predict mRS scores 3 and 6 months later, DWI stroke volume and FLAIR signal intensity; and (c) the PON1 Q192R variant has multiple effects on stroke outcomes that are mediated by its effects on antioxidant defenses and lipid peroxidation. Lipid peroxidation and lowered -SH and PON1-HDL activity are drug targets to prevent AIS and consequent neurodegenerative processes and increased oxidative reperfusion mediators due to ischemia-reperfusion injury.

Ischemic stroke with unknown onset of symptoms: current scenario and perspectives for the future.

Stroke is a major cause of disability worldwide and a neurological emergency. Intravenous thrombolysis and mechanical thrombectomy are effective in the reperfusion of the parenchyma in distress, but the impossibility to determine the exact time of onset was an important cause of exclusion from treatment until a few years ago. To review the clinical and radiological profile of patients with unknown-onset stroke, the imaging methods to guide the reperfusion treatment, and suggest a protocol for the therapeutic approach. The different imaging methods were grouped according to current evidence-based treatments. Most studies found no difference between the clinical and imaging characteristics of patients with wake-up stroke and known-onset stroke, suggesting that the ictus, in the first group, occurs just prior to awakening. Regarding the treatment of patients with unknown-onset stroke, four main phase-three trials stand out: WAKE-UP and EXTEND for intravenous thrombolysis, and DAWN and DEFUSE-3 for mechanical thrombectomy. The length of the therapeutic window is based on the diffusion weighted imaging-fluid-attenuated inversion recovery (DWI-FLAIR) mismatch, core-penumbra mismatch, and clinical core mismatch paradigms. The challenges to approach unknown-onset stroke involve extending the length of the time window, the reproducibility of real-world imaging modalities, and the discovery of new methods and therapies for this condition. The advance in the possibilities for the treatment of ischemic stroke, while guided by imaging concepts, has become evident. New studies in this field are essential and needed to structure the health care services for this new scenario.

Use of DWI-FLAIR Mismatch to Estimate the Onset Time in Wake-Up Strokes.

PurposeTo compare the MRI characteristics of patients with wake-up ischemic stroke (WUS) and with ischemic stroke with known onset time (clear-onset-time stroke, COS) to clarify the role of diffusion-weighted imaging–fluid-attenuated inversion recovery (DWI-FLAIR) mismatch in estimating the onset time of WUS patients.Patients and MethodsTwo hundred patients with acute ischemic stroke were selected for complete brain MRI within six hours of symptom onset, including DWI and FLAIR sequences. The patients were divided into WUS (n = 78) and COS (n = 122) groups, based on whether the time of onset was known. The general conditions and imaging characteristics were collected to compare the DWI-FLAIR mismatch features between the two groups at different time intervals.ResultsThere was no significant difference in the DWI-FLAIR mismatch on MRI within 2 hour after the first found abnormality between the two groups (50.0% vs 71.8%, p = 0.180). With increasing time, the DWI-FLAIR mismatch decreased substantially in the WUS group, while a higher DWI-FLAIR mismatch presence persisted in the COS group within a four-hour interval from the onset of symptoms to the MRI. The DWI-FLAIR mismatch was significantly lower in the WUS group than in the COS group from symptom identification to MRI at 2–3 h, 3–4 h, and 4–5 h intervals (15% vs 60%, 10.5% vs 48%, 6.7% vs 45.4%; p < 0.01).ConclusionOur results suggest that the presence of DWI-FLAIR mismatch within 2 h of the first found abnormality was not significantly different between WUS and COS. Therefore, Patients with WUS within 2 hours after the first detected abnormality may be suitable for intravenous thrombolysis.

Radiomic signature of DWI-FLAIR mismatch in large vessel occlusion stroke.

Ischemic diffusion-weighted imaging-fluid-attenuated inversion recovery (DWI-FLAIR) mismatch may be useful in guiding acute stroke treatment decisions given its relationship to onset time and parenchymal viability; however, it relies on subjective grading. Radiomics is an emerging image quantification methodology that may objectively represent continuous image characteristics. We propose a novel radiomics approach to characterize DWI-FLAIR mismatch. Ischemic lesions were visually graded for FLAIR positivity (absent, subtle, obvious) among consecutive large vessel occlusion stroke patients who underwent hyperacute MRI. Radiomic features were extracted from within the lesions on DWI and FLAIR. The DWI-FLAIR mismatch radiomics signature was built with features systematically selected by a cross-validated ElasticNet linear regression model of mismatch. We identified 103 patients with mean age 68±16 years; 63% were female. FLAIR hyperintensity was absent in 25%, subtle in 55%, and obvious in 20%. Inter-rater agreement for visual grading was moderate (Κ = .58). The radiomics signature of DWI-FLAIR mismatch included native FLAIR histogram kurtosis and local binary pattern-filtered FLAIR gray-level cluster shade; both correlated with visual grading (ρ = -.42, p<.001 and ρ = .40, p<.001, respectively). Radiomics can describe DWI-FLAIR mismatch and may provide objective, continuous biomarkers for infarct evolution using clinical-grade images. These novel biomarkers may prove useful for treatment decisions and future research.

Risk factors of ischemic stroke/transient ischemic attack in young women: A case report

This case report aims to demonstrate the clinical significance of the left internal carotid artery (ICA) hypoplasia in a young woman who received a combined oral contraceptive (COC) and its association with arterial occlusion and the development of a lacunar stroke/lacunar cerebral infarct (LACI). Brain magnetic resonance imaging (MRI) of the left frontal lobe revealed multiple subcortical and periventricular amplification/ischemia foci (49.0×17.0 mm), and lacunar infarct loci (2.0×4.0 mm). Brain magnetic resonance angiography revealed a markedly narrowed lumen of the left ICA (2.0–3.0 mm). MRI diffusion-weighted imaging-fluid attenuated inversion recovery revealed a moderate diffuse wall thickening and reinforcement of the left ICA. The patient was diagnosed with LACI and congenital hypoplasia of the left ICA and underwent antiplatelet drug therapy (aspirin - 100 mg) and a complete withdrawal of COC. A full amelioration of neurological symptoms was observed after one month of treatment.

DWI-FLAIR Mismatch-guided IVT is Safe and Effective in Treatment of AIS Beyond 4.5 Hours

Background: Perfusion or clinical mismatch imaging is useful in selecting patients with acute ischemic stroke (AIS) for reperfusion therapies beyond 4.5 hours. These techniques are expensive, technically difficult, and therefore unavailable in most settings. The diffusion weighted imaging-fluid attenuated inversion recovery (DWI-FLAIR) mismatch pattern has been studied only in wake-up stroke/stroke with unclear time of onset but not in AIS patients with clear time of onset of more than 4.5 hours. This study assesses routinely available magnetic resonance imaging (MRI) DWI-FLAIR sequences for selecting AIS patients for intravenous thrombolytic therapy (IVT) beyond 4.5 hours of the witnessed onset of symptoms. Aim: To study the clinical spectrum and outcome of patients with AIS who received IVT based on the DWI-FLAIR mismatch seen beyond 4.5 hours of symptom onset. Methods, Observation, and Results: Retrospective analysis was performed on 10 patients who received IVT for AIS beyond 4.5 hours and had an MRI DWI-FLAIR mismatch. In cohort study, 60% patients were males, with the median age of 59 years, the median baseline National Institutes of Health Stroke Scale (NIHSS) score of 10 (range 7 to 15), and the median time from the onset to imaging of 412.5 minutes. Within 24 hours of thrombolysis, improvement of &gt;4 points in NIHSS was seen in 7 out of 10 (70%) patients, and at the modified Rankin scale, the score of 0 to 1 was noted at 3 months in 8 out of 10 (80%) patients. Neuroimaging at 24 hours showed no intracerebral bleed. Discussion and Conclusion: DWI-FLAIR mismatch-guided IVT is safe and effective in patients with AIS beyond 4.5 hours of the onset of symptoms. More studies are recommended to confirm these findings.

Intravenous alteplase for stroke with unknown time of onset guided by advanced imaging: systematic review and meta-analysis of individual patient data

Patients who have had a stroke with unknown time of onset have been previously excluded from thrombolysis. We aimed to establish whether intravenous alteplase is safe and effective in such patients when salvageable tissue has been identified with imaging biomarkers. We did a systematic review and meta-analysis of individual patient data for trials published before Sept 21, 2020. Randomised trials of intravenous alteplase versus standard of care or placebo in adults with stroke with unknown time of onset with perfusion-diffusion MRI, perfusion CT, or MRI with diffusion weighted imaging-fluid attenuated inversion recovery (DWI-FLAIR) mismatch were eligible. The primary outcome was favourable functional outcome (score of 0-1 on the modified Rankin Scale [mRS]) at 90 days indicating no disability using an unconditional mixed-effect logistic-regression model fitted to estimate the treatment effect. Secondary outcomes were mRS shift towards a better functional outcome and independent outcome (mRS 0-2) at 90 days. Safety outcomes included death, severe disability or death (mRS score 4-6), and symptomatic intracranial haemorrhage. This study is registered with PROSPERO, CRD42020166903. Of 249 identified abstracts, four trials met our eligibility criteria for inclusion: WAKE-UP, EXTEND, THAWS, and ECASS-4. The four trials provided individual patient data for 843 individuals, of whom 429 (51%) were assigned to alteplase and 414 (49%) to placebo or standard care. A favourable outcome occurred in 199 (47%) of 420 patients with alteplase and in 160 (39%) of 409 patients among controls (adjusted odds ratio [OR] 1·49 [95% CI 1·10-2·03]; p=0·011), with low heterogeneity across studies (I2=27%). Alteplase was associated with a significant shift towards better functional outcome (adjusted common OR 1·38 [95% CI 1·05-1·80]; p=0·019), and a higher odds of independent outcome (adjusted OR 1·50 [1·06-2·12]; p=0·022). In the alteplase group, 90 (21%) patients were severely disabled or died (mRS score 4-6), compared with 102 (25%) patients in the control group (adjusted OR 0·76 [0·52-1·11]; p=0·15). 27 (6%) patients died in the alteplase group and 14 (3%) patients died among controls (adjusted OR 2·06 [1·03-4·09]; p=0·040). The prevalence of symptomatic intracranial haemorrhage was higher in the alteplase group than among controls (11 [3%] vs two [<1%], adjusted OR 5·58 [1·22-25·50]; p=0·024). In patients who have had a stroke with unknown time of onset with a DWI-FLAIR or perfusion mismatch, intravenous alteplase resulted in better functional outcome at 90 days than placebo or standard care. A net benefit was observed for all functional outcomes despite an increased risk of symptomatic intracranial haemorrhage. Although there were more deaths with alteplase than placebo, there were fewer cases of severe disability or death. None.

Diffusion-Weighted Imaging-Fluid-Attenuated Inversion Recovery Mismatch Is Associated with 90-Day Functional Outcomes in Patients Undergoing Mechanical Thrombectomy

Background and Purpose: Diffusion-weighted imaging-fluid-attenuated inversion recovery (DWI-FLAIR) mismatch is an early sign of acute ischemic stroke. DWI-FLAIR mismatch was reported to be valuable to select patients with unknown onset stroke who are eligible to receive intravenous thrombolysis (IVT), but its utility is less studied in patients undergoing mechanical thrombectomy (MT) for acute large vessel occlusion (LVO). We thus investigated the functional outcomes at 90 days between patients with DWI-FLAIR mismatch and those with match who underwent MT for LVO. Methods: We conducted a historical cohort study in consecutive patients who were evaluated by magnetic resonance imaging for suspected stroke at a single center. We enrolled patients with occlusion of internal carotid artery or horizontal or vertical segment of middle cerebral artery who underwent MT within 24 h after they were last known to be well. DWI-FLAIR mismatch was defined when a visible acute ischemic lesion was present on DWI without traceable parenchymal hyperintensity on FLAIR. Image analysis was done by 2 stroke neurologists independently. We estimated the adjusted odds ratio (OR) of DWI-FLAIR mismatch relative to DWI-FLAIR match for moderate outcome defined as modified Rankin Scale (mRS) 0–3, favorable outcome defined as mRS 0–2 and mortality at 90 days after the onset, and symptomatic intracranial hemorrhage (sICH) within 72 h after the onset. Results: Of the 380 patients who received MT, 202 were included. Patients with DWI-FLAIR mismatch (146 [72%]) had significantly higher baseline National Institutes of Health Stroke Scale (median 16 vs. 13, p = 0.01), more transferred-in (78 vs. 63%, p = 0.02), more IVT (45 vs. 18%, p = 0.0003), more cardioembolism (69 vs. 54%, p = 0.03), and shorter onset-to-hospital door times (median 175 vs. 371 min, p < 0.0001) than patients with DWI-FLAIR match. Patients with DWI-FLAIR mismatch had more moderate outcome than those with DWI-FLAIR match (61 vs. 52%, p = 0.24), and the adjusted OR was 3.12 (95% confidence interval [CI]: 1.35–7.19, p = 0.008). sICH within 72 h was less frequent in the DWI-FLAIR mismatch group (10 vs. 20%, p = 0.06), with an adjusted OR of 0.36 (95% CI: 0.13–0.97, p = 0.044). The adjusted ORs for favorable outcome and mortality were 0.87 (95% CI: 0.39–1.94, p = 0.73) and 0.63 (95% CI: 0.20–2.05, p = 0.44), respectively. Conclusions: DWI-FLAIR mismatch was associated with more moderate outcome and less sICH in the adjusted analysis in patients receiving MT for acute LVO. DWI-FLAIR mismatch could be useful to select patients with unknown onset stroke who are eligible to receive MT for acute LVO.

Abstract TP69: Association Between DWI-FLAIR Mismatch and Functional Outcomes in Patients Undergoing Mechanical Thrombectomy

Background and Purpose: Diffusion weighted imaging-fluid attenuated inversion recovery (DWI-FLAIR) mismatch was well recognized as an early sign of acute ischemic stroke lesions. In the era of mechanical thrombectomy (MT), DWI-FLAIR mismatch could be a good marker for candidates of MT. We thus investigated the association between DWI-FLAIR mismatch and functional outcomes in patients who received MT for acute large vessel occlusion (LVO). Methods: We conducted historical cohort study in consecutive patients who were evaluated by MRI for suspected stroke at single stroke center. We enrolled patients with occlusion of the ICA or M1 or M2 segment of MCA who were underwent MT within 24 hours after the last known to be well. FLAIR negative was defined when a visible acute ischemic lesion was present on DWI without traceable parenchymal hyperintensity on FLAIR. We estimated the adjusted OR of FLAIR negative for moderate outcome defined as mRS 0-3 at 90 days after onset. We also estimated the adjusted OR for symptomatic intracranial hemorrhage within 72 hours and mortality at 90 days. Results: Among 380 patients who received MT for acute LVO, 202 patients were included in this study. Patients with FLAIR negative was 146 (72%), and the rest were FLAIR positive. Patients with FLAIR negative had significantly higher baseline NIHSS (median 16 vs 13, p=0.01), more transferred-in (78% vs 63%, p=0.02), more intravenous thrombolysis (IVT) (45% vs 18%, P=0.0003), more cardioembolism (69% vs 54%, p=0.03), and shorter times from the onset to hospital door (median 175 vs 371 minutes, p&lt;0.0001). Patients with FLAIR negative had more moderate outcome than the counterparts (61% vs 52%, p=0.24). The adjusted OR of FLAIR negative compared to positive was 2.97 (95%CI, 1.33-6.60, p=0.008). Symptomatic intracranial hemorrhage within 72 hours was less frequent in the FLAIR negative group (10% vs 20%, p=0.06), with an adjusted OR of 0.34 (95%CI, 0.13-0.87, p=0.02). Conclusions: DWI-FLAIR mismatch was associated with better functional outcome in patients received MT for acute LVO at 90 days. DWI-FLAIR mismatch should be a good marker for the candidate of MT for acute LVO. Future randomized trial to evaluate the effectiveness of MRI-based MT using DWI-FLAIR mismatch should be considered.

Efficacy and Safety of Endovascular Thrombectomy for Ischemic Stroke in Nonagenarians

Introduction: Increased life expectancy results in a rapid increase of nonagenarian patients presenting with acute ischemic stroke (AIS) caused by large vessel occlusion (LVO). We conducted this study to assess the efficacy and safety of endovascular thrombectomy (ET) in this age group with use of imaging-based selection. Methods: We retrospectively analyzed clinical and imaging data from 2 different comprehensive stroke centers and compared the outcomes of ET versus intravenous thrombolysis (IVT) alone among eligible nonagenarians with LVO in anterior circulation and evidence of salvageable tissue on brain magnetic resonance imaging (MRI). Results: A total of 617 patients of AIS had been treated with IVT or ET, including 23 eligible nonagenarians. Among these, 9 patients were treated with IVT alone (IVT group) and 14 patients received ET group. Notably, the symptomatic intracranial hemorrhage rates were significantly lower after ET than after IVT (European-Australasian Acute Stroke Study II criteria, 0 vs. 33.3%; p = 0.047; National Institute of Neurological Disorders and Stroke criteria, 7.1 vs. 66.7%; p = 0.005). Moreover, although there were no statistically significant differences between the 2 groups on efficacy, ET tended to lead to greater early neurologic recovery at discharge (71.4 vs. 33.3%, p = 0.102) and improve functional outcome at 90 days (71.4 vs. 44.4%, p = 0.383), respectively. Conclusion: By using MRI-based selection, ET in nonagenarians with AIS caused by LVO within anterior circulation was safe and may lead to improve early neurologic recovery and functional independence at 90 days, as compared with IVT alone. Randomized trial in larger sample size testing efficacy of ET using diffusion-weighted imaging-fluid attenuated inversion recovery mismatch selection in this age group appears feasible.

Unknown-onset strokes with anterior circulation occlusion treated by thrombectomy after DWI-FLAIR mismatch selection.

The DAWN trial recently showed compelling evidence in treating late window and wake-up stroke patients with thrombectomy using a clinical-imaging mismatch. The aim was to evaluate the results of thrombectomy for unknown-onset strokes (UOS) treated in our centres after a diffusion weighted imaging/fluid attenuated inversion recovery (DWI-FLAIR) mismatch based selection. A multicentre, cohort study was performed of consecutive UOS treated by thrombectomy between 2012 and 2016. UOS with proximal anterior circulation occlusion discovered beyond 6 h from 'last seen normal' were compared with known-onset strokes (KOS) for whom thrombectomy was started within 6 h from onset. Time intervals were recorded from first time found abnormal. Results were adjusted for age, diabetes, hypertension, National Institutes of Health Stroke Scale, site of occlusion, DWI Alberta Stroke Programme Early CT Score, intravenous thrombolysis and use of general anaesthesia. Amongst 1246 strokes with anterior circulation occlusion treated by thrombectomy, 277 were UOS, with a 'last time seen well' beyond 6 h and DWI-FLAIR mismatch, and 865 were KOS who underwent groin puncture within 6 h. Favourable outcome was achieved less often in UOS than KOS patients (45.2% vs. 53.9%, P = 0.022). After pre-specified adjustment, this difference was not significant (adjusted relative risk 0.91; 95% confidence interval 0.80-1.04; P = 0.17). No differences were found in secondary outcomes. Time intervals from first found abnormal were significantly longer in UOS. Thrombectomy of UOS with anterior circulation occlusion and DWI-FLAIR mismatch appears to be as safe and efficient as thrombectomy of KOS within 6 h from onset. This pattern of imaging could be used for patient selection when time of onset is unknown.

MRI Assessment of Ischemic Lesion Evolution within White and Gray Matter

Background: In acute ischemic stroke (AIS), gray matter (GM) and white matter (WM) have different vulnerabilities to ischemia. Thus, we compared the evolution of ischemic lesions within WM and GM using MRI. Methods: From a European multicenter prospective database (I-KNOW), available T1-weighted images were identified for 50 patients presenting with an anterior AIS and a perfusion weighted imaging (PWI)/diffusion weighted imaging (DWI) mismatch ratio of 1.2 or more. Six lesion compartments were outlined: initial DWI (b = 1,000 s/mm²) lesion, initial PWI-DWI mismatch (T_max >4 s and DWI-negative), final infarct mapped on 1-month fluid-attenuated inversion recovery (FLAIR) imaging, lesion growth between acute DWI and 1-month FLAIR, DWI lesion reversal at 1 month and salvaged mismatch. The WM and GM were segmented on T1-weighted images, and all images were co-registered within subjects to the baseline MRI. WM and GM proportions were calculated for each compartment. Results: Fifty patients were eligible for the study. Median delay between symptom onset and baseline MRI was 140 min. The percentage of WM was significantly greater in the following compartments: initial mismatch (52.5 vs. 47.5%, p = 0.003), final infarct (56.7 vs. 43.3%, p < 0.001) and lesion growth (58.9 vs. 41.2%, p < 0.001). No significant difference was found between GM and WM percentages within the initial DWI lesion, DWI reversal and salvaged mismatch compartments. Conclusions: Ischemic lesions may extend preferentially within the WM. Specific therapeutic strategies targeting WM ischemic processes may deserve further investigation.

Diffusion-weighted imaging-fluid-attenuated inversion recovery mismatch is associated with better neurologic response to intravenous thrombolytic therapy in acute ischemic stroke patients.

ObjectiveTo investigate differences in the effect of intravenous (IV) thrombolysis regarding the mismatch of diffusion-weighted imaging–fluid-attenuated inversion recovery (DWI-FLAIR) among acute ischemic stroke patients who visited the emergency department (ED) within 3 hours from the onset of symptoms.MethodsAmong ED patients presenting with an acute ischemic stroke between January 2011 and May 2013 at a tertiary hospital, those who underwent magnetic resonance imaging before IV thrombolytic therapy were included in this retrospective study. Patients were divided into DWI-FLAIR mismatch and match groups. National Institutes of Health Stroke Scale (NIHSS) scores obtained initially, 24 hours after thrombolytic therapy, and on discharge, and early neurologic improvement (ENI) and major neurologic improvement (MNI) were compared.ResultsDuring the study period, 50 of the 213 acute ischemic stroke patients who presented to the ED were included. The DWI-FLAIR mismatch group showed a statistically significantly greater reduction in NIHSS both at 24 hours after thrombolytic therapy and upon discharge than did the match group (5.5 vs. 1.2, P<0.001; 6.0 vs. 2.3, P<0.01, respectively). Moreover, ENI and MNI were significantly greater for the DWI-FLAIR mismatch group than for the match group (27/36 vs. 2/14, P<0.001; 12/36 vs. 0/14, P=0.012, respectively).ConclusionAmong acute ischemic stroke patients who visited the ED within 3 hours from the onset of symptoms, patients who showed DWI-FLAIR mismatch showed a significantly better response to IV thrombolytic therapy than did the DWI-FLAIR match group in terms of neurologic outcome.

Are the current MRI criteria using the DWI-FLAIR mismatch concept for selection of patients with wake-up stroke to thrombolysis excluding too many patients?

BackgroundUp to 25% of stroke patients wake up with a neurological deficit, so called wake-up stroke (WUS). Different imaging approaches that may aid in the selection of patients likely to benefit from reperfusion therapy are currently under investigation. The magnetic resonance imaging (MRI) diffusion weighted imaging – fluid attenuated inversion recovery (DWI-FLAIR) mismatch concept is one proposed method for identifying patients presenting within 4.5 hours of the ischemic event.PurposeTo report our experience with the DWI-FLAIR mismatch concept for selection of wake-up stroke patients to be thrombolysed at our centre.Material and methodsPatients treated with off label intravenous thrombolysis (IVT) for WUS at our centre during a 6.5-month period were included. We performed MRI including DWI and FLAIR in all patients at admission. Each MRI examination was rated as either DWI-FLAIR mismatch or match. National Institutes of Health Stroke Scale (NIHSS) and modified Rankin Scale were used to measure clinical outcome. Cerebral computed tomography (CT) or MRI was performed within 24 hours after thrombolysis to determine the presence of any intracranial haemorrhage (ICH).ResultsTen patients treated with IVT for WUS were included. Four patients had a DWI-FLAIR mismatch and after IVT treatment the mean reduction in NIHSS in the DWI-FLAIR mismatch group was 4.0. In the DWI-FLAIR match group the mean reduction in NIHSS after IVT therapy was 4.8. None of the ten patients had any signs of ICH on follow-up imaging.ConclusionsIn this small series DWI-FLAIR mismatch was not associated with worse outcome or ICH. This suggests that selecting WUS patients using DWI-FLAIR mismatch in clinical trials may exclude a large group of patients who might benefit.

Abstract T P36: DWI Lesion Size but Not FLAIR Status Alone is Associated With Early Clinical Outcome in Stroke Patients Undergoing MRI Prior to Systemic Thrombolysis

Objectives: Treatment of ischemic stroke holds the risk of intracerebral hemorrhage (ICH) due to systemic thrombolysis, often associated with poor functional outcome. Hence, parameters allowing prediction from deleterious courses are of increasing interest. We have recently shown that fluid-attenuated inversion recovery (FLAIR)-positive lesions seen on baseline magnetic resonance imaging (MRI) are associated with an increased rate on ICH. This study asked for the relationship between findings originating from baseline MRI and the clinical course. Methods: Using a multi-parameter hospital-based registry, the diffusion-weighted imaging (DWI) and FLAIR on baseline MRI of 122 ischemic stroke patients were analyzed for DWI lesion size and FLAIR-positive lesions within diffusion-restricted areas. These data originated from MRI that had been done prior to treatment with tissue plasminogen activator (tPA) within 3 hours from symptom onset, whereas computed tomography performed within 24 hours post-treatment served for detection of ICH. The early clinical outcome was assessed at hospital discharge using Barthel index (BI), modified Rankin scale (mRS) and National Institutes of Health Stroke Scale (NIHSS). Results: Out of 97 patients providing sufficient imaging quality, FLAIR-positive lesions were present in 25 patients (25.8 %) and ICH occurred in 32 patients (33.0 %). Remarkably, patients with or without FLAIR-positive lesions did not differ concerning the clinical outcome (BI, P =0.055; mRS, P =0.106; NIHSS, P =0.295). Patients exhibiting an initial DWI lesion size of at least 1/3 of vascular territory demonstrated an increased NIHSS ( P =0.031), increased mRS ( P =0.011) and decreased BI ( P =0.004) when compared to patients with smaller lesion sizes. As expected, more severe clinical affection was found in patients suffering from ICH (BI, P =0.013; mRS, P =0.001; NIHSS, P =0.016). Conclusions: In ischemic stroke patients treated with tPA, initial DWI lesion size was found to be closely associated with early clinical outcome, which was, however, not seen for FLAIR positivity. Therefore, a combination of both DWI lesion size and FLAIR status might represent an addition tool to enhance safety for stroke patients undergoing systemic thrombolysis.

Wake-up stroke: clinical characteristics, imaging findings, and treatment option - an update.

About 25% of all strokes occur during sleep, i.e., without knowledge of exact time of symptom onset. According to licensing criteria, this large group of patients is excluded from treatment with received tissue-plasminogen activator, the only specific stroke treatment proven effective in large randomized trials. This paper reviews clinical and imaging characteristics of wake-up stroke and gives an update on treatment options for these patients. From clinical and imaging studies, there is evidence suggesting that many wake-up strokes occur close to awakening and thus, patients might be within the approved time-window of thrombolysis when presenting to the emergency department. Several imaging approaches are suggested to identify wake-up stroke patients likely to benefit from thrombolysis, including non-contrast CT, CT-perfusion, penumbral MRI, and the recent concept of diffusion weighted imaging-fluid attenuated inversion recovery (DWI-FLAIR). A number of small case series and observational studies report results of thrombolysis in wake-up stroke, and no safety concerns have occurred, while conclusions on efficacy cannot be drawn from these studies. To this end, there are ongoing clinical trials enrolling wake-up stroke patients based on imaging findings, i.e., the DWI-FLAIR-mismatch (WAKE-UP) or penumbral imaging (EXTEND). The results of these trials will provide evidence to guide thrombolysis in wake-up stroke and thus, expand treatment options for this large group of stroke patients.

Abstract W P44: Can Diffusion-Weighted Imaging-Fluid-Attenuated Inversion Recovery Mismatch (Positive Diffusion-Weighted Imaging/ Negative Fluid-Attenuated Inversion Recovery) at 3 Tesla Identify Patients With Stroke at &lt;4.5 Hours?

Background: and Purpose_At 1.5 T, diffusion-weighted imaging-fluid-attenuated inversion recovery (DWI-FLAIR) mismatch helps identify strokes within 4.5 hours of onset. However, at 3T, studies have found divergent results. The goal of this study was to determine whether DWI-FLAIR mismatch at 3T would also be helpful for identifying patients within 4.5 hours of symptom onset. Methods: All patients presenting with an ischemic stroke in the middle cerebral artery territory and explored with 3T MRI within 12 hours between November 2007 and April 2012 were included in this retrospective study. Two readers analyzed the DWI and FLAIR images. Logistic regression was performed to determine independent predictors of FLAIR visibility. Also, the predictive values of a mismatch for identifying patients with stroke onset ≤4.5 hours were estimated. Results: The study included 194 patients. The only predictive factor of FLAIR visibility was delayed MRI acquisition. The DWI-FLAIR mismatch was able to identify patients within 4.5 hours of stroke onset with relatively low sensitivity (0.55; 95% confidence interval, 0.48-0.63), low specificity (0.60; 95% confidence interval, 0.42-0.77), high positive predictive value (0.88; 95% confidence interval, 0.82-0.94), and very low negative predictive value (0.19; 95% confidence interval, 0.11-0.28). In addition, 44.5% of patients had a positive FLAIR sequence within 4.5 hours. Conclusions: This study improves our understanding of DWI-FLAIR mismatch as an imaging biomarker for wake-up management of patients with stroke. At 3T, the presence of a DWI-FLAIR mismatch was able to identify stroke onset of &lt;4.5 hours. However, 44.5% of such stroke cases demonstrated FLAIR signal changes.

Can Diffusion-Weighted Imaging–Fluid-Attenuated Inversion Recovery Mismatch (Positive Diffusion-Weighted Imaging/Negative Fluid-Attenuated Inversion Recovery) at 3 Tesla Identify Patients With Stroke at &lt;4.5 Hours?

At 1.5 T, diffusion-weighted imaging-fluid-attenuated inversion recovery (DWI-FLAIR) mismatch helps identify strokes within 4.5 hours of onset. However, at 3T, studies have found divergent results. The goal of this study was to determine whether DWI-FLAIR mismatch at 3T would also be helpful for identifying patients within 4.5 hours of symptom onset. All patients presenting with an ischemic stroke in the middle cerebral artery territory and explored with 3T MRI within 12 hours between November 2007 and April 2012 were included in this retrospective study. Two readers analyzed the DWI and FLAIR images. Logistic regression was performed to determine independent predictors of FLAIR visibility. Also, the predictive values of a mismatch for identifying patients with stroke onset ≤4.5 hours were estimated. The study included 194 patients. The only predictive factor of FLAIR visibility was delayed MRI acquisition. The DWI-FLAIR mismatch was able to identify patients within 4.5 hours of stroke onset with relatively low sensitivity (0.55; 95% confidence interval, 0.48-0.63), low specificity (0.60; 95% confidence interval, 0.42-0.77), high positive predictive value (0.88; 95% confidence interval, 0.82-0.94), and very low negative predictive value (0.19; 95% confidence interval, 0.11-0.28). In addition, 44.5% of patients had a positive FLAIR sequence within 4.5 hours. This study improves our understanding of DWI-FLAIR mismatch as an imaging biomarker for wake-up management of patients with stroke. At 3T, the presence of a DWI-FLAIR mismatch was able to identify stroke onset of <4.5 hours. However, 44.5% of such stroke cases demonstrated FLAIR signal changes.

Diffusion-weighted Imaging–Fluid Attenuated Inversion Recovery Mismatch in Nocturnal Stroke Patients with Unknown Time of Onset

More than a quarter of patients with ischemic stroke (IS) are excluded from thrombolysis because of an unknown time of symptom onset. Recent evidence suggests that a mismatch between diffusion-weighted imaging (DWI) and fluid attenuated inversion recovery (FLAIR) imaging could be used as a surrogate for the time of stroke onset. We compared used the DWI-FLAIR mismatch and the FLAIR/DWI ratio to estimate the time of onset in a group of patients with nocturnal strokes and unknown time of onset. We used a prospectively collected acute IS patient database with MRI as the initial imaging modality. Nineteen selected nocturnal stroke patients with unknown time of onset were compared with 22 patients who had an MRI scan within 6 hours from stroke onset (control A) and 19 patients who had an MRI scan between 6 and 12 hours (control B). DWI and FLAIR signal was rated as normal or abnormal. FLAIR/DWI ratio was calculated from independent DWI and FLAIR ischemic lesion volumes using semiautomatic software. The DWI-FLAIR mismatch was different among groups (unknown 43.7%; control A 63.6%; control B 10.5%; Fisher-Freeman-Halton test; P = .001). There were significant differences in FLAIR/DWI ratio among the 3 groups (unknown 0.05 ± 0.12; control A 0.17 ± 0.15; control B 0.04 ± 0.06; Kruskal-Wallis test; P < .0001). Post-hoc pairwise comparisons revealed that FLAIR/DWI ratio from the unknown group was significantly different from the control B group (P = .0045) but not different from the control A group. DWI volumes were not different among the 3 groups. A large proportion of patients with nocturnal IS and an unknown time of stroke initiation have a DWI-FLAIR mismatch, suggesting a recent onset of stroke.